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Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female

Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently is...

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Autores principales: Barillari, Maria Rosaria, Karali, Marianthi, Di Iorio, Valentina, Contaldo, Maria, Piccolo, Vincenzo, Esposito, Maria, Costa, Giuseppe, Argenziano, Giuseppe, Serpico, Rosario, Carotenuto, Marco, Cappuccio, Gerarda, Banfi, Sandro, Melillo, Paolo, Simonelli, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306489/
https://www.ncbi.nlm.nih.gov/pubmed/32596134
http://dx.doi.org/10.1016/j.ymgmr.2020.100615
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author Barillari, Maria Rosaria
Karali, Marianthi
Di Iorio, Valentina
Contaldo, Maria
Piccolo, Vincenzo
Esposito, Maria
Costa, Giuseppe
Argenziano, Giuseppe
Serpico, Rosario
Carotenuto, Marco
Cappuccio, Gerarda
Banfi, Sandro
Melillo, Paolo
Simonelli, Francesca
author_facet Barillari, Maria Rosaria
Karali, Marianthi
Di Iorio, Valentina
Contaldo, Maria
Piccolo, Vincenzo
Esposito, Maria
Costa, Giuseppe
Argenziano, Giuseppe
Serpico, Rosario
Carotenuto, Marco
Cappuccio, Gerarda
Banfi, Sandro
Melillo, Paolo
Simonelli, Francesca
author_sort Barillari, Maria Rosaria
collection PubMed
description Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNHL) and early onset Retinitis Pigmentosa (RP) that may clinically overlap with Usher syndrome. Genetic testing by clinical exome sequencing identified two variants in PEX1: the missense variant c.274G > C; p.(Val92Leu) that was already reported in a PBD patient, and the variant c.2140_2145dup; p.(Ser714_Gln715dup) which is a novel, non-frameshift variant, absent in control databases. On the basis of the molecular analysis, a thorough clinical examination revealed nail and dental abnormalities, a mild cognitive impairment, learning disabilities and poor feeding, apart from the retinal and audiological features initially identified. The clinical and molecular findings led us to the diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes.
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spelling pubmed-73064892020-06-25 Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female Barillari, Maria Rosaria Karali, Marianthi Di Iorio, Valentina Contaldo, Maria Piccolo, Vincenzo Esposito, Maria Costa, Giuseppe Argenziano, Giuseppe Serpico, Rosario Carotenuto, Marco Cappuccio, Gerarda Banfi, Sandro Melillo, Paolo Simonelli, Francesca Mol Genet Metab Rep Case Report Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNHL) and early onset Retinitis Pigmentosa (RP) that may clinically overlap with Usher syndrome. Genetic testing by clinical exome sequencing identified two variants in PEX1: the missense variant c.274G > C; p.(Val92Leu) that was already reported in a PBD patient, and the variant c.2140_2145dup; p.(Ser714_Gln715dup) which is a novel, non-frameshift variant, absent in control databases. On the basis of the molecular analysis, a thorough clinical examination revealed nail and dental abnormalities, a mild cognitive impairment, learning disabilities and poor feeding, apart from the retinal and audiological features initially identified. The clinical and molecular findings led us to the diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes. Elsevier 2020-06-20 /pmc/articles/PMC7306489/ /pubmed/32596134 http://dx.doi.org/10.1016/j.ymgmr.2020.100615 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Barillari, Maria Rosaria
Karali, Marianthi
Di Iorio, Valentina
Contaldo, Maria
Piccolo, Vincenzo
Esposito, Maria
Costa, Giuseppe
Argenziano, Giuseppe
Serpico, Rosario
Carotenuto, Marco
Cappuccio, Gerarda
Banfi, Sandro
Melillo, Paolo
Simonelli, Francesca
Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female
title Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female
title_full Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female
title_fullStr Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female
title_full_unstemmed Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female
title_short Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female
title_sort mild form of zellweger spectrum disorders (zsd) due to variants in pex1: detailed clinical investigation in a 9-years-old female
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306489/
https://www.ncbi.nlm.nih.gov/pubmed/32596134
http://dx.doi.org/10.1016/j.ymgmr.2020.100615
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